Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting
2018; Cell Press; Volume: 175; Issue: 4 Linguagem: Inglês
10.1016/j.cell.2018.09.009
ISSN1097-4172
AutoresMerav Cohen, Amir Giladi, Anna-Dorothea Gorki, Dikla Gelbard Solodkin, Mor Zada, Anastasiya Hladik, Ádám Miklósi, Tomer‐Meir Salame, Keren Bahar Halpern, Eyal David, Shalev Itzkovitz, Tibor Harkany, Sylvia Knapp, Ido Amit,
Tópico(s)Renal and related cancers
ResumoLung development and function arises from the interactions between diverse cell types and lineages. Using single-cell RNA sequencing (RNA-seq), we characterize the cellular composition of the lung during development and identify vast dynamics in cell composition and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, innate lymphocytes (ILCs), and basophils. Using interleukin (IL)-33 receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and granulocyte-macrophage colony-stimulating factor (GM-CSF), characterized by unique signaling of cytokines and growth factors important for stromal, epithelial, and myeloid cell fates. Antibody-depletion strategies, diphtheria toxin-mediated selective depletion of basophils, and co-culture studies show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole-tissue signaling interaction map on the single-cell level can broaden our understanding of cellular networks in health and disease.
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